1. Technical Field
The present disclosure relates to improved enteral nutritional compositions comprising docosahexaenoic acid (DHA) and arachidonic acid (ARA) and also to methods for providing nutritional support in the form of a stabilized emulsion to a population of subjects suffering from nutritional deficiencies, such as preterm and/or low-birth-weight infants. The liquid nutritional composition of the present disclosure may contain a lipid component that contains an emulsion of DHA and/or arachidonic acid (ARA) that is dispersed in an aqueous component comprising nutrients such as amino acids, vitamins, minerals and additional nutrients, or combinations of the foregoing. The nutritional composition may be suitable for enteral delivery via nasogastric tube, intragastric feeding, transpyloric administration and/or any other means of administration that results in the introduction of the nutritional composition directly into the digestive tract of a subject. In some embodiments, the nutritional composition is a fortifier suitable for addition to human milk or infant formula for oral feeding.
2. Background Art
The present disclosure relates to an improved enteral nutritional composition that addresses nutritional deficiencies in ill populations as well as physiological and other consequences often arising from those deficiencies. In particular, the disclosure addresses nutritional deficiencies that may arise in preterm and/or low-birth-weight infants.
Nutritional support for a preterm infant is of great importance since short-term survival and long-term growth and development are at stake. Important goals when providing nutritional support to preterm infants include promoting growth rates and nutrient accretion that are equivalent to those achieved during fetal development, thereby optimizing neurodevelopmental outcomes and laying strong foundations for long-term health. These goals are not easily attained, as the critically ill, low-birth-weight, premature infant often cannot tolerate traditional enteral feeding due to concomitant pathologies or immaturity of the intestinal tract and other organ systems. Thus, total parenteral nutrition (TPN) is indicated as either the only or the preferred method of providing nutrition support. And although TPN can be life saving, it is not a perfect means of nutritional support. TPN lacks many critical nutrients, and its limitations may have long-lasting physiological and developmental consequences for infants.
Low-birth-weight and very-low-birth-weight infants are particularly susceptible to both postnatal growth failure and nutrient deficiencies. Yet, TPN fails to provide an adequate supply of valuable nutrients, such as docosahexaenoic acid and/or arachidonic acid. Accordingly, many preterm infants do not receive an adequate supply of DHA and/or ARA.
In healthy subjects consuming a normal diet, wherein the normal diet provides sufficient DHA and ARA, there is generally no need for DHA or ARA supplementation because considerable amounts of both ARA and DHA are deposited in the human brain and other tissues during intrauterine and postnatal growth. (Clandinin M T et al., “Requirements of newborn infants for long chain polyunsaturated fatty acids”. Acta Paediatr Scand 1989; 351 Suppl: 63-71.) In fact, the fetus accumulates long chain polyunsaturated fatty acids (LCPUFAs) such as DHA and ARA during the last trimester of pregnancy, as the placenta provides the fetus with DHA and ARA. (A. Lapitlonne et. Al, “Reevaluation of the DHA requirement for the premature infant” Prostaglandins, Leukotrienes and Essential Fatty Acids 81 (2009) 143-150.) But in cases of preterm birth, an infant faces the sudden loss of the placental LCPUFA supply. Premature infants are often critically ill and face numerous physiological stresses that may rapidly exhaust their available LCPUFA stores, and the resulting LCPUFA deficit may increase the more premature the infant.
Meeting the nutritional needs of preterm infants is problematic due to their gastrointestinal immaturity, poor nutrient stores and the high demand for nutrients to support growth. (L. G. Smithers et al., “Effect of two doses of docosahexaenoic acid (DHA) in the diet of preterm infants on infant fatty acid status: Results from the DINO trial”, Prostaglandins, Leukotrienes and Essential Fatty Acids 79 (2008) 141-146.) Yet, in critically ill, preterm infants, it appears that an inadequate supply of essential fatty acids and their derivatives may lead to long-term impairments in visual function and in neurodevelopment. (D. Driscoll et al., “Pharmaceutical and clinical aspects of parenteral lipid emulsions in neonatology”, Clinical Nutrition (2008) 27, 497-503.) These problems are exacerbated by the absence of long-chain polyunsaturated acids, such as DHA and ARA, in parenteral nutrition and TPN solutions.
Indeed, TPN and other parenteral nutritional supplements that are currently on the market provide, at best, only negligible amounts of preformed DHA and ARA. DHA is an omega-3-fatty acid and is the most abundant long chain polyunsaturated fatty acid in the brain and retina and is thought to be essential for proper brain and vision development of infants. Although a metabolic pathway exists for biosynthesis from dietary linolenic acid, the pathway is bioenergetically unfavorable, and mammals obtain most of their DHA from preformed DHA provided via dietary sources. For infants, then, the source of DHA is typically human milk; however, DHA is typically absent from parenteral formulas provided to preterm infants.
Parenteral formulas also generally fail to provide sufficient amounts of arachidonic acid. ARA is an omega-6 LCPUFA that serves a major role as a structural lipid associated with phospholipids in the blood, liver, muscle and other major organ systems. ARA is synthesized by the elongation and desaturation of linoleic acid. However, most ARA must be provided in the diet. ARA is especially important during periods of rapid body growth, and is, therefore, an important component of infant nutrition.
Numerous studies have indicated that unsupplemented preterm milk provided to infants provides inadequate quantities of several nutrients required to meet the needs of preterm infants (Davis, D. P., “Adequacy of expressed breast milk for early growth of preterm infants”, Archives of Disease in Childhood, 52, p. 296-301, 1997). While exact needs vary among infants due to differences in activity, energy expenditure, efficiency of nutrient absorption, illness and the ability to utilize energy for tissue synthesis, presently available parenteral nutritional sources are inadequate.
Moreover, feeding volume is often not well tolerated in preterm infants, and nutrients must be provided in an acceptable volume, often via enteral administration. An appropriate method of enteral feeding for a preterm infant is based on gestational age, birth weight, clinical condition and on the opinion of presiding medical personnel. Specific feeding decisions are made based on an infant's ability to coordinate sucking, swallowing and breathing. Frequently, preterm infants or infants who are less mature, weak or critically ill require feeding by tube to avoid risks of aspiration and to conserve energy.
Nasogastric feedings are commonly used in neonatal intensive care units and may be accomplished with bolus or continuous infusions of fortified human milk or other nutritional supplements. Continuous feedings may be better tolerated by very low birth weight infants and infants who have not previously tolerated bolus feedings; however, as previously discussed, reduced or deficient nutrient delivery is a problem associated with continuous feeding methods known in the art.
Therefore, there is a need for stable nutritional compositions that are well-tolerated by preterm infants and that can be easily administered to subjects suffering from nutritional deficiencies in forms and manners that are readily accepted by the subject and the caregiver.
Populations, such as preterm infants, often suffer nutritional deficiencies because they are provided with diets lacking critical nutrients as described above. Thus, a need exists in the art to provide a nutritional composition comprising valuable nutrients that support infant development, such as DHA and ARA. Therefore, the nutritional compositions and methods of the present disclosure provide enteral nutritional support to subjects suffering from nutritional deficiencies in order to promote optimum health and development by delivering important nutrients that are either absent from or provided in inadequate amounts in parenteral nutrition and other infant formulas.